Is DSTYK p.Ser916Phe (c.2747C>T) pathogenic?

DSTYK p.Ser916Phe (c.2747C>T) is classified Likely benign in DSTYK (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-12). AlphaMissense: likely benign (0.0871); Rare (popmax 0.237%, afr).

How common is DSTYK p.Ser916Phe (c.2747C>T) in the general population?

DSTYK p.Ser916Phe (c.2747C>T) is rare (popmax 0.237%, afr) (gnomAD).

What do computational predictors say about DSTYK p.Ser916Phe (c.2747C>T)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

DSTYK p.Ser916Phe

c.2747C>T · rs151054719 · VCV2071647

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.237%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -8.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.52 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 154 bp · p 0.89 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.237% African / African-American · 178/75,048 alleles

Filtering AF 0.209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.198%

Overall 0.0128% 206/1,613,748 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.237%	422
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0288%	3,472
Admixed American	0.00833%	12,002
European (non-Finnish)	0.000254%	393,216

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DSTYK
Protein: p.Ser916Phe
Coding: c.2747C>T
MANE Select: NM_015375
dbSNP: rs151054719
Type: single nucleotide variant
Location: chr1:205147601 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 916: a UniProt-annotated variant site (in cakut1; uncertain significance)

Full DSTYK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSTYK p.Ala206Val Uncertain significance ★★ ⚠ same type
DSTYK p.Ala477Ser Uncertain significance ★★ ⚠ same type
DSTYK p.Ala601Val Uncertain significance ★★ ⚠ same type
DSTYK p.Arg411Gln Uncertain significance ★★ ⚠ same type
DSTYK p.Arg462Gln Uncertain significance ★★ ⚠ same type
DSTYK p.Arg471Gln Uncertain significance ★★ ⚠ same type
DSTYK p.Arg626Gln Uncertain significance ★★ ⚠ same type
DSTYK p.Arg635His Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dstyk-p-ser916phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown